Combination Therapies in the Treatment of Primary Liver Cancers

Abstract

Several combined treatment strategies have been used in the treatment of hepatocellular carcinoma (HCC). These include various combinations of locoregional interventions as well as the association of locoregional and systemic therapies. Radio-frequency ablation (RFA) is currently accepted as the best therapeutic choice for nonsurgical patients with early-stage HCC. Nevertheless, the rate of complete tumor eradication is highly dependent on tumor size and presence of large abutting vessels. Several attempts have been made to increase the effect of RFA in HCC treatment. Given that HCC is mostly nourished by the hepatic artery, a combination of RFA and balloon catheter occlusion of the tumor arterial supply or prior transcatheter arterial embolization or chemoembolization has been used to increase heat efficiency. A different strategy is to adominister intrarterially an embolic, drug-eluting bead (DEB) within 24 h of RFA to take advantage of the reactive hyperemia induced by RFA to facilitate delivery of the microspheres to the tumor-bearing area. Investigators have also suggested the combined use of percutaneous approaches, such as ethanol injection and RFA. Despite the advances in locoregional treatments, long-term outcomes of patients with early or intermediate-stage HCC remain unsatisfactory because of the high rate of tumor recurrence. To date, studies of sorafenib, a tyrosine kinase inhibitor with anti-angiogenetic properties, have demonstrated its efficacy in advanced HCC; however, there may also be a role for this agent – or other molecular targeted drugs – in earlier-stage disease, either as adjuvant treatment after curative therapy or in combination with trans-arterial chemoembolization.